It is already known in the industries such as pharmaceutical, health food and agrichemical industries that a film-forming composition is applied to solid preparations such as tablets and granules. It is applied in order to shield the solid preparations from light, prevent them from oxidation, adhesion and moisture, give them storage stability, sustain the release of a drug, or mask an unpleasant taste or odor.
Examples of the film-forming composition include cellulose derivatives such as water-soluble hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxyethyl methyl cellulose and hydroxyethyl ethyl cellulose. The other examples include pullulan, carrageenan and polyvinyl alcohol. It is known that coating is carried out by applying an aqueous solution of such a film-forming composition to a preparation.
Hydroxypropyl methyl cellulose having a reduced molecular weight is used widely for coating tablets or granules with water-soluble nonionic cellulose ether. It also exhibits excellent stability as it is left standing so that it has been in wide use mainly as a film-coating agent in recent years. However, preparations coated with such a water-soluble polymer leave an unpleasant taste such as bitterness peculiar to a drug when they are administered as a pharmaceutical or health food because the film easily dissolves in the oral cavity. In addition, the unpleasant taste lowers the compliance of patients with administration. Moreover, administration of preparations coated with a water-soluble base material may give a sticky or slimy feel to patients and therefore become a unpleasant burden to them.
Masking of a bitter taste with a large amount of a sweetener or the like can be given as a method for overcoming such a problem. However, it does not have a sufficient effect. Filling of a drug in a hard capsule can also be given as a countermeasure, but children and the aged encounter difficulty in taking such a drug.
As another method, use of a base material forming a water-insoluble coating film is proposed. Use of a synthetic polymer such as vinyl acetate resins or acrylic resins, or emulsion thereof is provided. However, there is a problem that a monomer remaining in such a synthetic polymer is sometimes toxic or interaction between the monomer and a coated preparation may deteriorate the stability of the film. According to Japanese Patent Application Unexamined Publication (Toku-Hyo) No. 2000-509399, an acrylic resin is used as an example of the synthetic polymer. According to Japanese Patent No. 3193041, an acrylic resin and an enteric cellulose ester are shown as an example of a water-insoluble film. According to Japanese Patent No. 3350059, an acrylic resin is used as a water-insoluble film for an outer layer of granules containing, in the core thereof, a water-swelling polymer.
Use of water-insoluble ethyl cellulose or an enteric base material such as hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate or carboxymethyl ethylcellulose as a cellulose derivative closer to a natural material is proposed in order to solve the above-described problems. When such a base material is used singly, its water insolubility contributes to excellent masking of taste, but decrease in the elution of a drug may prevent the achievement of the intended bioavailability. In addition, since the property of an enteric base material depends on pH, a difference in the pH in the digestive tracts between individuals may lead to uneven elution of a drug. Use of water-insoluble ethyl cellulose is described in Japanese Patent No. 2836493.
As another example, use of a water-insoluble wax, oil or fat, higher alcohol or fatty acid for lowering the elution of a drug is described in Japanese Patent Application Unexamined Publication No. 2005-82594.
An application of a mixture with water-soluble hydroxypropylmethyl cellulose in order to improve the elution is described in Japanese Patent Application Examined Publication No. 7-74151/1995. However, it is difficult to control the mixing and to obtain both good masking of taste and desired elution at the same time. In general, a water-insoluble coating base material is required to be dissolved in an organic solvent prior to application. Accordingly, there is an environmental problem of removing the organic solvent to the air by drying or a problem of a residual solvent in the preparation.